DNA methylation provides a signature to identify cell type. Previous data shows that DNA methylation signature of bulk tumors reveals important classification information that is not available using current standard pathological methods (histologic interpretation by a pathologist). In this project, we will extend this concept by analyzing the DNA methylation signatures of individual cells within the tumor. The analysis of single-cell methylation will then enable a cell-by-cell determination of differentiation and heterogeneity within the tumor. It will also allow characterization of the tumor microenvironment, which is emerging as a critically important component for new therapeutic modalities, including immunotherapy.